Validation of a novel framework defining the acceptable standard of care for heart failure with reduced ejection fraction

Abstract

Abstract Background In heart failure with reduced ejection fraction (HFrEF), uptitration of neurohormonal antagonists to trial-proven doses shown to reduce mortality is challenging and seldomly achieved in clinical practice. A major reason for underdosing of these agents is the lack of a clear description of what constitutes an acceptable standard of care in HFrEF. To address this limitation, a novel framework for describing the physician adherence to evidence-based treatment was recently proposed. The aim of our study was to evaluate and validate the proposed framework in a real-world population of patients with HFrEF. Methods A cohort of patients with HFrEF, defined as left ventricular ejection fraction (LVEF) <40%, under treatment with neurohormonal antagonists for at least 3 months were retrospectively identified at a tertiary hospital's Heart Failure Clinic. Demographic, clinical, echocardiographic and treatment data were assessed. Patients were divided in three strata for each neurohormonal antagonist, according to the proposed framework: Status I – patients receiving target doses or the highest tolerated dose; Status II – use of subtarget doses for reasons unrelated to clinically important intolerance; and Status III – not receiving the drug at any dose. The prognostic value of each strata was assessed for all-cause mortality. Results A total of 408 patients (mean age 68±12 years, 78% male, 63% ischemic etiology) were included. The median LVEF was 31% (IQR 25–36) and most patients were in NYHA class II or III [210 (51.5%) and 163 (40%), respectively]. Medical therapy is described in Table 1. During a median follow-up of 3.3 years (IQR 1.4–5.6), 210 patients died. On univariable analysis, achieving Status I of beta-blocker (BB) therapy (HR: 0.50; 95% CI: 0.32–0.81; P=0.004) or ACEi/ARB (HR: 0.56; 95% CI: 0.36–0.86; P=0.012) was associated with reduced all-cause mortality. The mortality of patients in Status II of BB or ACEi/ARB was similar to the mortality of those not receiving the drug (HR for BB: 0.90; 95% CI: 0.53–1.52; P=0.69 and HR for ACEi/ARB: 0.71; 95% CI: 0.42–1.18; P=0.182) – figure 1. Achieving Status I of BB remained independently associated with reduced mortality after adjustment for several clinical and echocardiographic confounders (n=13) (adjusted HR: 0.59; 95% CI: 0.35–0.98; P=0.041). Conclusions In this real-world population of patients with HFrEF, the vast majority of patients were in Status I of BB and ACEi/ARB therapy. Achieving Status I of BB therapy seems to be associated with reduced mortality, even after adjustment for several markers of disease severity, highlighting the need for uptitration of medical therapy to maximal tolerated doses according to trial-proven regimens. Funding Acknowledgement Type of funding sources: None.